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Zusammenfassung: Eine 68-jährige Patientin stellte sich mit seit 10 Monaten bestehender rechtsseitiger Epiphora, blutiger Sekretion und Schwellung im Bereich des Tränensacks vor. Im CT zeigte sich eine weichteildichte Raumforderung des rechten Tränensacks mit Erweiterung des knöchernen Ductus nasolacrimalis. Durch externe Dakryozystorhinostomie mit inzisionaler Biopsie konnte die Diagnose eines malignen Melanoms gestellt werden. Nach dem Staging erfolgte die weitere Therapie mit Exenteratio orbitae, lateraler Rhinotomie, En-Bloc-Resektion der Tränenwege und adjuvanter Radioimmuntherapie. Ein Jahr postoperativ ist die Patientin rezidiv- und metastasenfrei.

Hintergrund: Mortalität und Delirinzidenz werden beim kritisch kranken Patienten durch das Analgosedierungsregime beeinflusst. Je tiefer die Sedierung, je höher die Dosis applizierter Analgetika, desto schwieriger ist die Einschätzung von Schmerz und Sedierungsgrad. Daher gewinnen apparative Messverfahren, wie die Messung der Reizschwelle des nozizeptiven Flexorenreflexes (NFRT), zunehmend an Bedeutung. Ziel der Arbeit: Ziel der vorliegenden Studie ist es, eine mögliche Assoziation zwischen der Höhe des nozizeptiven Flexorenreflexes, der Mortalität und dem Auftreten eines Delirs zu untersuchen. Material und Methodik: Durch die retrospektive Analyse eines 57 Intensivpatienten umfassenden Pilotdatensatzes der interdisziplinären operativen Intensivstation des Universitätsklinikums Ulm, erhoben zwischen November 2018 und März 2020, wurde in einem adjustierten logistischen Regressionsmodell eine mögliche Assoziation zwischen NFRT, Mortalität und Delirinzidenz berechnet. Je nach Cut-off-Wert ergeben sich Reizschwellenkorridore mit folgenden Vergleichspaaren: < 20 mA vs. 20–40 mA/20–50 mA/20–60 mA, > 40 mA vs. 20–40 mA, > 50 mA vs. 20–50 mA, > 60 mA vs. 20–60 mA. Die Ergebnisdarstellung erfolgt als Odds Ratios, bereinigt um Alter, Geschlecht, Größe, TISS-28, SAPS II, RASS, BPS und die verwendeten Analgetika. Die Schmerzerfassung erfolgte in der untersuchten Gruppe standardisiert mittels der Behavioral Pain Scale sowie ergänzend durch die NFRT-Messung. Ergebnisse: Es konnte eine statistisch nicht signifikante Tendenz zu einer Mortalitätszunahme bei einer NFRT > 50 mA gegenüber dem Reizschwellenkorridor von 20–50 mA ermittelt werden (OR 3.3, KI: 0,89–12.43, p= 0,07). Eine Tendenz zu einer Reduktion der Delirhäufigkeit trat bei einer NFRT < 20 mA gegenüber einem Reizschwellenkorridor von 20–40 mA auf (OR 0.40, KI: 0,18–0,92, p= 0,03). Diskussion: Anhand der Höhe der NFRT kann zum aktuellen Zeitpunkt keine Empfehlung zur Anpassung des verwendeten Analgosedierungsregimes beim kritisch kranken, nichtmitteilungsfähigen Intensivpatienten gegeben werden. Die Beobachtung einer Tendenz hin zu einer Zunahme der Mortalität bei hohen Reizschwellen bzw. einer Reduktion des Auftretens eines Delirs bei niedrigen Reizschwellen muss in standardisierten Studien überprüft werden.

Zusammenfassung: Angioödeme mit Beteiligung der Lippen, der Zunge sowie der pharyngealen und laryngealen Schleimhaut treten selten als Komplikation einer Therapie mit ACE-Hemmern auf, können aber zu akuter Atemnot bis hin zum Tod durch Ersticken führen.Wir berichten über eine 83-jährige Patientin, bei der eine derartige Atemwegsproblematik zunächst durch Notfalltracheotomie beherrscht wurde, es im weiteren Verlauf jedoch zu einer lebensbedrohlichen Dislokation der Trachealkanüle mit nachfolgendem Spannungspneumothorax kam.Anhand des Falles werden die möglichen Folgen einer Trachealkanülendislokation diskutiert und die Vorteile der frühzeitigen Anlage eines epithelisierten Tracheostomas aufgezeigt, das nach akzidenteller Dekanülierung jederzeit ein sicheres und schnelles Wiedereinführen der Trachealkanüle erlaubt.Damit wird eine rasche Sicherung der Atemwege gewährleistet, selbst bei fehlender oro- oder nasotrachealer Intubationsmöglichkeit aufgrund einer Verlegung der oberen Atemwege oder erschwerten Intubationsbedingungen.

We have compared regulation of the serglycin gene in human erythroleukemia (HEL) and CHRF 288-11 cells, which have megakaryocytic characteristics, with promyelocytic HL-60 cells. Deletion constructs were prepared from the region -1123/+42 to -20/+42, and putative regulatory sites were mutated. In all three cell lines, the two major regulatory elements for constitutive expression were the (-80)ets site and the cyclic AMP response element (CRE) half-site at -70. A protein from HEL and CHRF, but not HL60, nuclear extracts bound to the (-80)ets site. Another protein from all three cell lines bound to the (-70)CRE. Phorbol 12-myristate 13-acetate (PMA) and dibutyryl cyclic AMP (dbcAMP) increased expression of the reporter in HEL cells 2.5-3- and 4.5-fold, respectively, from all constructs except those with (-70)CRE mutations. PMA virtually eliminated expression of serglycin mRNA and promoter constructs, but dbcAMP increased expression in HL-60 cells. The effects of PMA and dbcAMP on promoter expression correlated with mRNA expression. The strengths of two DNase I-hypersensitive sites in the 5'-flanking region and the first intron in all three cells correlated with relative endogenous serglycin mRNA expression. An additional DNase I-hypersensitive site in HL60 DNA in the first intron may be related to the high serglycin expression in HL60 relative to HEL or CHRF cells.

Proteoglycan-binding peptides were designed based on consensus sequences in heparin-binding proteins: XBBXBX and XBBBXXBX, where X and B are hydropathic and basic residues, respectively. Initial peptide constructs included (AKKARA)(n) and (ARKKAAKA)(n) (n = 1-6). Affinity coelectrophoresis revealed that low M(r) peptides (600-1,300) had no affinities for low M(r) heparin, but higher M(r) peptides (2,000-3,500) exhibited significant affinities (K(d) congruent with 50-150 nM), which increased with peptide M(r). Affinity was strongest when sequence arrays were contiguous and alanines and arginines occupied hydropathic and basic positions, but inclusion of prolines was disruptive. A peptide including a single consensus sequence of the serglycin proteoglycan core protein bound heparin strongly (K(d) congruent with 200 nM), likely owing to dimerization through cysteine-cysteine linkages. Circular dichroism showed that high affinity heparin-binding peptides converted from a charged coil to an alpha-helix upon heparin addition, whereas weak heparin-binding peptides did not. Higher M(r) peptides exhibited high affinities for total endothelial cell proteoglycans (K(d) congruent with 300 nM), and approximately 4-fold weaker affinities for their free glycosaminoglycan chains. Thus, peptides including concatamers of heparin-binding consensus sequences may exhibit strong affinities for heparin and proteoglycans. Such peptides may be applicable in promoting cell-substratum adhesion or in the design of drugs targeted to proteoglycan-containing cell surfaces and extracellular matrices.

Abstract:  The case of a 50-year-old man with an unusual sinus of the styloid process is presented. This anomaly caused recurrent otorrhea and repeated neck inflammation. The sinus was identified in the upper part of the styloid process and was resected completely as definitive treatment. Since the styloid process is formed by mesenchymal tissue of the second branchial arch, lack of chondrification and ossification was presumed to be the cause of the sinus found in the patient. In case of direct communication between the styloid process cavity and the middle ear space the term “styloid process recess” is suggested. This recess can act as a possible source for recurrent middle ear infections and neck inflammations.

Synthesis of sulphated proteoglycans was compared in human erythroleukaemia (HEL) cells grown under control conditions and under stimulation by dimethyl sulphoxide (DMSO) and phorbol 12-myristate 13-acetate (PMA). Synthesis of [35S]sulphate-labelled proteoglycans by DMSO-treated cells was decreased by about 35% relative to controls, but synthesis of proteoglycans by PMA-treated cells increased 3-4-fold. Control and DMSO-treated cells secreted 65% of the newly synthesized proteoglycans, but PMA-treated cells secreted more than 90%. Sepharose CL-6B chromatography and SDS/PAGE suggested the presence of several proteoglycans in the cells and culture medium. The PMA-treated cells synthesized a low-Mr proteoglycan (Kav. 0.3(that was not present in controls and DMSO-treated cultures. The proteoglycans of the cells and medium from control, DMSO-treated and PMA-treated cultures could be separated into three fractions by octyl-Sepharose chromatography. The proteoglycans were resistant to trypsin but were degraded by Pronase and papain to fragments similar in size to the NaOH/NaBH4-generated glycosaminoglycans. The average chain length of the glycosaminoglycans (Kav. 0.20 on Sepharose CL-6B for controls) was decreased by DMSO (Kav. 0.25) and by PMA (Kav. 0.30-0.38). Chondroitin ABC lyase digestion of the proteoglycans from the medium of the control cultures produced two core proteins at Mr 31,000 and 36,000. The DMSO medium proteoglycans had only the 31,000-Mr core protein, and the PMA culture medium proteoglycans had core proteins of Mr 27,000, 31,000 and 36,000. Changes in synthesis of proteoglycans induced by DMSO or PMA may have relevance for the maturation of haematopoietic cells.

The three-dimensional structure of Aspergillus niger pectin lyase B (PLB) has been determined by crystallographic techniques at a resolution of 1.7 A. The model, with all 359 amino acids and 339 water molecules, refines to a final crystallographic R factor of 16.5%. The polypeptide backbone folds into a large right-handed cylinder, termed a parallel beta helix. Loops of various sizes and conformations protrude from the central helix and probably confer function. The largest loop of 53 residues folds into a small domain consisting of three antiparallel beta strands, one turn of an alpha helix, and one turn of a 3(10) helix. By comparison with the structure of Erwinia chrysanthemi pectate lyase C (PelC), the primary sequence alignment between the pectate and pectin lyase subfamilies has been corrected and the active site region for the pectin lyases deduced. The substrate-binding site in PLB is considerably less hydrophilic than the comparable PelC region and consists of an extensive network of highly conserved Trp and His residues. The PLB structure provides an atomic explanation for the lack of a catalytic requirement for Ca2+ in the pectin lyase family, in contrast to that found in the pectate lyase enzymes. Surprisingly, however, the PLB site analogous to the Ca2+ site in PelC is filled with a positive charge provided by a conserved Arg in the pectin lyases. The significance of the finding with regard to the enzymatic mechanism is discussed.

This study has examined changes in proteoglycan synthesis during megakaryocyte maturation in vivo. Guinea pigs were injected with Na235SO4, and megakaryocytes and platelets were isolated from 3 h to 5 days later. The proteoglycans and other sulfated molecules in both cells were characterized at each time point by gel filtration, ion-exchange chromatography, gel electrophoresis, and chemical and enzymatic digestions. Two populations of chondroitin 6-sulfate proteoglycans were found by DEAE-Sephacel chromatography. The major fraction was eluted with 4 M guanidine hydrochloride and the minor fraction with 4 M guanidine HCl, 2% Triton X-100. The Kav of the major proteoglycan peak in the platelets at 1 day after injection was 0.18-0.20 on Sepharose CL-6B and decreased gradually to 0.12 by 3 days, when proteoglycan radioactivity per cell was maximal. The peak for megakaryocyte proteoglycans at 3 h was broad, with Kav = 0.1-0.2. The appearance of different portions of the proteoglycan peak in platelets coincided with their disappearance from megakaryocytes. Proteoglycan size was a function of glycosaminoglycan chain length. The proteoglycans eluted with Triton X-100 from DEAE-Sephacel (Kav = 0.04-0.07 on Sepharose CL-6B) were not labeled in platelets until 2 days after injection. Our data suggest that megakaryocytes synthesize different-sized chondroitin sulfate proteoglycans at different stages of development. The proteoglycans of the major fraction were released from platelets in response to thrombin, and a small amount was released by ADP. The proteoglycans of the Triton X-100 eluate were not released by thrombin or ADP. About 20% of the sulfate radioactivity was incorporated into molecules that appear to be sulfated proteins and were not released by thrombin or ADP.

Abstract: Sinus thrombosis has rarely been associated with closed head injury; more often, thrombosis of the sigmoid or transverse sinus is caused by otogenic inflammations or tumours, or occurs during pregnancy. Symptoms are frequently vague, while untreated thrombus progression may be fatal due to venous congestion and infarction. We report a 32-year-old man presenting with right hearing loss, tinnitus and headache 2 days after a closed head injury. Neurological examination showed no additional abnormality. The EEG showed focal bifrontal slowing. CT revealed a fracture of the occipital bone. MRI and MRA demonstrated complete thrombosis of the right sigmoid and transverse sinuses. After 2 weeks of intravenous heparin therapy followed by warfarin, the patient's hearing improved and MRI and MRA showed complete recanalisation of the sigmoid and transverse sinuses. Venous sinus thrombosis can be an undetected sequel to head injury. Appropriate imaging studies should be carried out to enable therapy to be started as soon as possible.

We prospectively compared pregnancy outcome after exposure to sumatriptan with that of disease-matched controls and nonteratogen controls. There were no differences in the rates of live births, spontaneous abortions, therapeutic abortions, or major birth defects among the three groups. This first prospective report suggests that the use of sumatriptan during organogenesis is not associated with an apparent increased risk of major birth defects.

Abstract: We describe an unusual occult transclival cerebrospinal fluid (CSF) fistula to the sphenoid sinus demonstrated by MRI. CT was performed because of a posterior cerebral infarct caused by cardiac arrhythmia. Axial sections showed fluid in the sphenoid sinus. High-resolution scans revealed a bony defect 3 mm in diameter of the posterior wall of the sphenoid sinus, and MRI showed a transclival CSF fistula. This occult lesion was confirmed by surgery and duraplasty was successfully performed via an endonasal approach.

Experiments with subcutaneous oil injections have been frequently tried. The first clinical observations were published in 1869. Extensive animal experiments were carried out by Leube in 1895 and by Mills in Lusk's laboratory in 1911. Both considered oil injections were of practical value. Others have repeated this work using fat and oil for injections with varying degree of success. Winternitz was, for instance, unable to obtain good results.We resorted to this method of treatment in a very serious case of Hirschsprung's disease (child 11 years of age). Following the total extirpation of the colon and sigmoid the child either refused or vomited most of his food. He also had loose stools. His condition was desperate, his weight having fallen from 63 to 47 pounds, a loss of 16 pounds.The first two days we injected 50 cc. of sterile cotton seed oil. The child gained in weight, but after stopping the injections the weight remained stationary. For the following seven days we increased the amount of oil to 100 cc. per day. The general condition and appetite improved to such an extent that he took food by mouth better than before. His weight likewise increased.Again the injections were discontinued, with the same effect upon his gaining, namely, almost no rise. We therefore decided to continue the oil injections for fifteen days more. Simultaneously the weight rose. As the child was eating well and his state of nutrition was much improved, we have discontinued the oil injections.Apparently the greater part of the oil was absorbed, but there are a few areas of swelling undoubtedly due to the oil. Over a period of forty-one days thirty injections of oil were given. The total amount was 2250 gm., equal to 20,475 calories or 500 calories per day (750 nem).